Trial Outcomes & Findings for Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation (NCT NCT03513328)
NCT ID: NCT03513328
Last Updated: 2023-09-15
Results Overview
Assess the MED of thiotepa in combination with reduced-dose busulfan, fludarabine and rATG required to achieve engraftment in \>90% subjects undergoing hematopoietic stem cell transplantation for non-malignant disorders.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
6 participants
Primary outcome timeframe
Day 42
Results posted on
2023-09-15
Participant Flow
Subjects were enrolled from June 2018 through January 2021. Only Arm A enrolled patients due to change in clinical practice. No donors with HLA mismatch enrolled in this study.
Participant milestones
| Measure |
Group A--Thiotepa Single Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
6
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
Baseline characteristics by cohort
| Measure |
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
—
|
—
|
—
|
4 Participants
n=5 Participants
|
4 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
—
|
—
|
—
|
2 Participants
n=5 Participants
|
2 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=21 Participants
|
|
Age, Continuous
|
—
|
—
|
—
|
13 years
n=5 Participants
|
13 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
—
|
—
|
—
|
6 Participants
n=5 Participants
|
6 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
—
|
—
|
—
|
2 Participants
n=5 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
—
|
—
|
—
|
4 Participants
n=5 Participants
|
4 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
—
|
—
|
—
|
6 participants
n=5 Participants
|
6 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 42Population: MED dose of thiotepa in group A was determined to be 5 mg/kg in combination with Fludarabine and rATG. All six patients engrafted by day 42 using this dose. No subsequent escalation was done.
Assess the MED of thiotepa in combination with reduced-dose busulfan, fludarabine and rATG required to achieve engraftment in \>90% subjects undergoing hematopoietic stem cell transplantation for non-malignant disorders.
Outcome measures
| Measure |
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Assessment of Minimum Effective Dose (MED) of Thiotepa
|
5 mg/kg
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 42; Day 365Population: Risk of rejection was determined in Group A. None of the patients rejected the graft = 0% (95% CI 0-46%) either at Day 42 or Day 365
Percentage of all subjects who initiated conditioning regimen and have sustained engraftment failure.
Outcome measures
| Measure |
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Percentage of Subjects With Graft Rejection/Failure.
|
0 Percentage of participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Month 24Population: At 24 month OS and DFS was 100% (95% CI 54-100%) in group A, the OS and DFS could not have been evaluated for group B due to lack of enrollment
Percentage of subjects who initiated conditioning regimen and are without evidence of underlying disease (DFS).
Outcome measures
| Measure |
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Percentage of Subjects Without Disease Recurrence Who Are Alive at 24 Months Post Transplant
|
100 Percentage of patients
Interval 54.0 to 100.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Month 24Population: At 24 month OS and DFS was 100% (95% CI 54-100%) in group A, the OS and DFS could not have been evaluated for group B due to lack of enrollment
Percentage of subjects who initiated conditioning regimen and are alive at 24 months post transplant (OS).
Outcome measures
| Measure |
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Percentage of Subjects Alive at 24 Months Post Transplant (OS)
|
100 Percentage of patients
Interval 54.0 to 100.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Month 12Population: Transplant related mortality at 12 months post transplant was 0% (95% CI 0-46%) in Group A. Transplant-related mortality could not have been evaluated for group B due to lack of enrollment
Percentage of subjects who initiated conditioning regimen and who died due to a cause unrelated to the underlying disease.
Outcome measures
| Measure |
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Evaluation of Transplant-related Mortality
|
0 Percentage of patients
Interval 0.0 to 46.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Month 12Population: 1 of 6 patients developed GVHD grade 2-4.
Graft-versus host disease symptoms measured using Modified Glucksberg Staging Criteria. (Scale 0-4; with 4 being most severe)
Outcome measures
| Measure |
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Number of Participants With Grade 2-4 Acute Graft-versus-host Disease (GVDH)
|
1 Number of patients
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Month 24Population: cGVHD in 2 of 6 participants
Measures the frequency of chronic graft-vs-host disease in Group A participants
Outcome measures
| Measure |
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Percentage of Participants With Chronic Graft-versus-host Disease (cGVHD)
|
33 Percentage of patients
Interval 0.4 to 78.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: Percentages of patient at risk for complications during first 2 years post transplant
Complications gathered via CIBMTR (Center for International Blood \& Marrow Transplant Research) post-transplant form was tabulated and described by treatment received.
Outcome measures
| Measure |
Group A--Thiotepa Single Dose
n=6 Participants
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Percentage of Participants With Transplant-related Complications
Mucositis - 1st year post transplant
|
100 Percentage of patients
Interval 54.0 to 100.0
|
—
|
—
|
—
|
|
Percentage of Participants With Transplant-related Complications
Viral reactivations - first year post transplant
|
67 Percentage of patients
Interval 22.0 to 96.0
|
—
|
—
|
—
|
|
Percentage of Participants With Transplant-related Complications
Covid 19 Infection first year post transplant
|
17 Percentage of patients
Interval 0.0 to 64.0
|
—
|
—
|
—
|
|
Percentage of Participants With Transplant-related Complications
Bacterial Infection first year post transplant
|
33 Percentage of patients
Interval 0.0 to 78.0
|
—
|
—
|
—
|
|
Percentage of Participants With Transplant-related Complications
Hemorrhagic Cystitis in first year post transplant
|
17 Percentage of patients
Interval 0.0 to 64.0
|
—
|
—
|
—
|
|
Percentage of Participants With Transplant-related Complications
Viral reactivations in 2nd year post transplant
|
67 Percentage of patients
Interval 22.0 to 96.0
|
—
|
—
|
—
|
|
Percentage of Participants With Transplant-related Complications
Covid 19 infection in the 2nd year post transplant
|
17 Percentage of patients
Interval 0.0 to 64.0
|
—
|
—
|
—
|
|
Percentage of Participants With Transplant-related Complications
Bacterial Infections in the 2nd year post transplant
|
17 Percentage of patients
Interval 0.0 to 64.0
|
—
|
—
|
—
|
Adverse Events
Group A--Thiotepa Single Dose
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Group A--Thiotepa Escalated Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Group B--Thiotepa Single Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Group B--Thiotepa Escalated Dose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group A--Thiotepa Single Dose
n=6 participants at risk
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group A--Thiotepa Escalated Dose
Fully matched 10/10 subjects with lower risk of graft failure. Subjects will undergo 10/10 HLA (human leukocyte antigen) matched bone marrow and peripheral blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
Group B--Thiotepa Single Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of single daily dose thiotepa (5 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--single daily dose: Conditioning regimen for hematopoietic stem-cell transplant. Single daily IV dose of Thiotepa at 5 mg/kg.
|
Group B--Thiotepa Escalated Dose
Subjects with higher risk of graft failure. Subjects will undergo transplant with \<10/10 bone marrow or peripheral blood match, or receiving cord blood transplant. Subjects receive combination of escalated dose of thiotepa (10 mg/kg)added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG).
Thiotepa--escalated dose: Twice daily IV dose of Thiotepa at 5 mg/kg, twelve hours apart, 10mg/kg total.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Mucositis
|
50.0%
3/6 • Number of events 3 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
|
Infections and infestations
Salmonella Bacteremia
|
16.7%
1/6 • Number of events 1 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
|
Infections and infestations
Coag Negative Staph Bacteremia
|
16.7%
1/6 • Number of events 1 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
|
Renal and urinary disorders
Haemorrhagic Cystitis
|
16.7%
1/6 • Number of events 1 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
|
Vascular disorders
Deep Vein Thrombosis
|
16.7%
1/6 • Number of events 1 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
|
Immune system disorders
Fever and joint pain
|
16.7%
1/6 • Number of events 1 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress secondary to mucositis
|
16.7%
1/6 • Number of events 1 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
|
Investigations
Tranaminitis
|
16.7%
1/6 • Number of events 1 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
|
Gastrointestinal disorders
Dehydration
|
16.7%
1/6 • Number of events 1 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
—
0/0 • First 100 days post transplant and AESI for 24 months.
Grade III and higher adverse events and serious adverse events were monitored for first 100 days. All-Cause Mortality and AESI were monitored for 24 months.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place